Summer’s coming to a close and the patient sitting in your office is worried. A bad cough and wheeze sent him to the hospital for three days last winter, and he feels like he’s never quite gotten back to normal. He stopped smoking a few years ago, and uses the long-acting bronchodilators and inhaled corticosteroids you prescribed. But he still worries about another COPD exacerbation; it seems like each time he gets sick, it’s more difficult to recover. Is there anything else he can do to make it less likely he’ll get sick again this year?
The answer, according to a study published in this week’s NEJM, is yes. Azithromycin taken daily for a year decreased the frequency of COPD exacerbations and improved quality of life in a cohort with COPD, reports Richard Albert and colleagues.
Why azithromycin? The macrolide antibiotic has anti-inflammatory and immune-modulatory benefits (which is why it is given to patients with cystic fibrosis and bronchiectasis) on top of its antibiotic action. However, studies have been split on the question of whether long-term antibiotics benefit patients with COPD.
Enter the current study, which enrolled 1,142 patients with COPD from 12 academic centers across the United States. To be eligible for the study, all patients either used continuous supplemental oxygen or had suffered a COPD exacerbation in the past year that required systemic steroids, a visit to the ED or hospitalization. Approximately 80 percent were receiving inhaled corticosteroids and/or long-acting bronchodilators. (Patients with prolonged QTc or hearing loss were excluded from the study – as these are known to be adverse effects associated with azithromycin).
Participants were randomly assigned to take either azithromycin at a 250 mg daily dose or a placebo pill for a year. Those with daily azithromycin stayed exacerbation-free for a significantly longer time: 266 days prior to first exacerbation versus 174 days for those with placebo. There was no statistically significant difference in mortality.
The daily antibiotic also helped patients’ quality of life, as measured by a commonly used survey which asks about symptoms, activity level and overall comfort. However, taking an antibiotic daily does not come without risk.
The biggest concern, of course, is increasing microbial resistance. To investigate this question, each patient had nasopharyngeal swabs taken at study visits. More patients in the azithromycin group became colonized with bacteria that were resistant to macrolide antibiotics, but this finding didn’t have any clear clinical significance. It remains unknown what this resistance pattern could mean for patients’ families or community.
Hearing loss was also a potential issue. More patients taking azithromycin than placebo experienced a decrement in their hearing over the year.
In an accompanying editorial, Nikolaos M. Siafakis, a pulmonologist who is the president of the European Respiratory Society, balanced these risks and benefits, and wrote that the study data come out in favor of azithromycin: “The findings of Albert and co-workers…in my opinion turns the balance towards the benefits of azithromycin treatment. However, if azithromycin is going to be used in patients known to be frequent COPD exacerbators, then the local antibiotic resistance patterns should be closely monitored…On balance however the long term use of azithromycin to prevent AECOPD seems to be a risk in accord with the classical advice of Hippocrates – do good – no harm.”
Question: Would you put the patient in question on long-term azithromycin based on this study?